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Early-life vancomycin treatment promotes airway inflammation and impairs microbiome homeostasis

机译:早期万古霉素治疗可促进气道炎症并损害微生物组稳态

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摘要

Several studies have reported that gut and lung microbiomes are involved in the process of asthma pathogenesis. However, it remains unclear how perinatal or early-life antibiotic intervention affect adult allergic airway inflammation. We assigned C57BL/6 mice randomly to four experimental groups: normal saline control (NS), ovalbumin (OVA), vancomycin pretreated NS (VAN-NS), and vancomycin pretreated OVA (VAN-OVA). The vancomycin groups were orally given the drug from gestational day 14 to 6 week. An OVA-induced asthma model was then established at 6 weeks of age, and airway inflammation was evaluated. In addition, total DNA was extracted from the feces and lung tissue and used for 16S rDNA gene sequencing, to detect the composition of the microbiome. In the VAN-OVA group, airway inflammation and Th2-related cytokines were found to be significantly increased versus the control groups. Gene sequencing showed that vancomycin treatment attenuated the richness and evenness, and altered the composition of the microbiome in the gut and lung. Micrococcaceae and Clostridiaceae-1 were potentially correlated to the severity of allergic airway inflammation. Our study suggests that perinatal and early-life vancomycin intervention aggravates allergic inflammation in adulthood, which might be correlated with imbalanced gut and lung microbiome homeostasis.
机译:几项研究报告说,肠道和肺部微生物群与哮喘的发病机理有关。但是,尚不清楚围产期或生命早期的抗生素干预如何影响成人变应性气道炎症。我们将C57BL / 6小鼠随机分为四个实验组:生理盐水对照(NS),卵清蛋白(OVA),万古霉素预处理的NS(VAN-NS)和万古霉素预处理的OVA(VAN-OVA)。从妊娠第14天到第6周口服万古霉素组药物。然后在6周龄时建立OVA诱发的哮喘模型,并评估气道炎症。另外,从粪便和肺组织中提取总DNA,并用于16S rDNA基因测序,以检测微生物组的组成。在VAN-OVA组中,与对照组相比,发现气道炎症和Th2相关细胞因子显着增加。基因测序表明,万古霉素治疗减弱了丰富度和均匀度,并改变了肠道和肺中微生物组的组成。微球菌科和梭菌-1可能与过敏性气道炎症的严重程度相关。我们的研究表明,围产期和生命早期的万古霉素干预会加重成年期的过敏性炎症,这可能与肠道和肺微生物组稳态失衡有关。

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